A Revised Hemodynamic Theory of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression.

TrendsThe choroid is an anatomically unique vascular bed that provides essential trophic support to the retina.Alterations in choroidal anatomy and hemodynamics are strongly associated with the development of age-related macular degeneration (AMD), the leading cause of blindness in the industrialized world.Rather than a passive conduit to flow, the vascular endothelium is highly active and strongly influenced by local blood flow.A variety of AMD-associated signaling pathways are hemodynamically regulated in the vascular endothelium.A revised model of choroidal hemodynamics as an underlying cause of AMD pathogenesis is emerging, wherein local hemodynamic parameters influence choroidal and retinal pigmented epithelial cell health.